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Researchers Developing A Novel Human Nerve Cell Model.

BONN, Germany, May 14, 2019 -- Nerve cells derived from human stem cells often serve as the basis for research into brain diseases.

However, these cells differ considerably in their quality and produce varying results.

Scientists around the world are therefore looking for simple cell models that lead to consistent results when an experiment is repeated.

In two studies, research teams from the University of Bonn, the Vrije Universiteit Amsterdam, and the Max Planck Institute for Experimental Medicine in Gottingen describe a model derived from stem cells that consists of only one human nerve cell.

It was obtained from pluripotent stem cells through a fast forward programming method and provides highly standardized conditions for investigating nerve cell functions.

Using cell reprogramming, induced pluripotent stem cells (iPS cells) can be generated from a blood or skin sample.

The body cells are reset into an embryonic stage and are then able to differentiate further into a huge variety of cell types again such as heart muscle or brain cells.

The expectations are high.

"Nerve cells produced from iPS cells are nowadays the most attractive tool for research into brain diseases and pharmaceutical research," said Oliver Brustle of the University Hospital Bonn (UKB).

Human nerve cells derived from iPS cells can vary considerably.

Depending on the cell culture method and production route chosen, they react very differently in experiments.

"However, we are looking for a cell model that is able to produce the same results when an experiment is repeated," said Michael Peitz.

The results of the studies should be statistically verified.

For this reason, the UKB scientists, together with the Max Planck Institute (MPI) for Experimental Medicine in Gottingen and the Vrije Universiteit Amsterdam, developed and tested a cell culture model consisting of a single nerve cell obtained from human iPS cells via a highly standardized cell programming method.

This "single" sits on glial cells, which are natural neighbors of nerve cells and crucial for their maintenance and function.

The nerve cell is talking to itself

The "single" brain cells talks to itself because its main nerve fiber (axon) ends up connecting to processes of the same nerve cell.

"In principle, it's a single neurons with a shortcircuit," said Kristina Rehbach, one of the lead authors at the UKB.

This allows the scientists to eavesdrop on the "single" nerve cell chatting with itself.

The circular signal transmission between the axon and the respective neuron takes place via synapses.

These are interfaces at which electrical signals cause the release of messenger substances, which again lead to electrical impulses on the receiver side. Here the signals can be amplified or reduced.

The scientists tested how this single-cell model behaves in stimulation experiments.

They used both neurons responsible for excitation in the brain as well as inhibitory nerve cells.

"We were able to demonstrate that this model, which consists of only a single nerve cell, yields highly reproducible data in the functional tests and thus represents a very good basis for high-throughput experiments," said Matthijs Verhage from the Vrije Universiteit Amsterdam.

The research team sees many possible applications for the "single" nerve cell model. It can be used to study disease mechanisms.

"For example, if a protein at a synapse is altered by a gene mutation, the consequences for signal transmission can be observed directly in this model," said Brustle.

Another advantage is that iPS cells reprogrammed from the skin or blood of patients can be used to generate neurons with disease- and patient-specific features.

The cell model could of particular interest for pharmaceutical research because it is standardized, scalable and applicable to a wide variety of brain diseases.

Citation: Marieke Meijer et al., A Single-Cell Model for Synaptic Transmission and Plasticity in Human iPSC-Derived Neurons. Cell Reports, 2019; 27 (7): 2199 DOI: 10.1016/j.celrep.2019.04.058

Abstract/Article: http://bit.ly/2Vw5Ppx

Contact: Matthijs Verhage, matthijs@cncr.vu.nl

Citation: Hong Jun Rhee et al., An Autaptic Culture System for Standardized Analyses of iPSC-Derived Human Neurons. Cell Reports, 2019; 27 (7): 2212 DOI: 10.1016/j.celrep.2019.04.059

Abstract/Article: http://bit.ly/2VvF3Om

Contact: Jeong Seop Rhee, rhee@em.mpg.de
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Publication:Stem Cell Research News
Geographic Code:4EUGE
Date:May 20, 2019
Words:692
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